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Benjamin W. Y. Lo, Hitoshi Fukuda, Satoru Miyawaki, Anderson C. O. Tsang, Masaomi Koyanagi
  1. McGill University Health Centre, Montreal, Quebec, Canada
  2. Department of Neurosurgery, Kochi University, Kochi
  3. Faculty of Medicine, The University of Tokyo, Tokyo
  4. Department of Surgery, Division of Neurosurgery, Queen Mary Hospital, University of Hong Kong, Hong Kong
  5. Amagasaki General Medical Center, Kyoto University, Hyogo, Japan

DOI:10.25259/SNI-74-2019

Copyright: © 2019 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Y. Lo BW, Fukuda H, Miyawaki S, O. Tsang AC, Koyanagi M. Short review of randomized controlled trials for Surgical Neurology International: Part II - drain-associated cerebrospinal fluid infections. Surg Neurol Int 26-Mar-2019;10:39

How to cite this URL: Y. Lo BW, Fukuda H, Miyawaki S, O. Tsang AC, Koyanagi M. Short review of randomized controlled trials for Surgical Neurology International: Part II - drain-associated cerebrospinal fluid infections. Surg Neurol Int 26-Mar-2019;10:39. Available from: http://surgicalneurologyint.com/surgicalint-articles/9245/

Date of Submission
13-Feb-2019

Date of Acceptance
15-Feb-2019

Date of Web Publication
26-Mar-2019

INTRODUCTION

Two methodologically sound randomized controlled trials (RCTs) were published in the third and fourth quarters of 2018 dealing with drain-associated cerebrospinal fluid (CSF) infections. Both RCTs offer significant scientific findings which may be of interest to readers of Surgical Neurology International.

Infectious diseases society of America’s 2017 clinical infectious disease guidelines for external ventricular drains

Drain-associated CSF infections have a pooled incidence rate of about 11.4/1000 catheter days.[ 10 ] The Infectious Diseases Society of America’s 2017 Clinical Infectious Disease Guidelines for external ventricular drains are listed in Table 1 .[ 10 ]


Table 1

Infectious Diseases Society of America’s 2017 Clinical Infectious Disease guidelines for external ventricular drains.

 

Infections due to external ventricular drains and lumbar drains

Most infections related to external ventricular or lumbar drains are introduced at the time of drain placement, whereas retrograde infection is another, very secondary mechanism of contamination. Risk factors for ventriculostomy-associated CSF infections include (1) previous craniotomy, (2) systemic infection, (3) skull fracture with CSF leak, (4) intraventricular/subarachnoid hemorrhage, (5) increased duration of drain, and (6) procedural factors (e.g., drain site leaks, lack of tunneling, multiple catheter irrigations, and increased frequency of CSF sampling).[ 1 , 5 , 8 ]

Use and efficacy of prophylactic antibiotics

Prophylactic antimicrobial agents have not been shown to significantly reduce drain-associated CSF infections in patients without significant risk factors.[ 10 ] Prior systematic review demonstrated the effectiveness of silver coated ventricular catheters in preventing ventriculostomy-associated infections.[ 1 , 5 , 8 ] Even though antimicrobial-impregnated catheters may increase the number of false negative culture results, the following two 2018 RCTs offer some insight regarding two methods for infection prevention. The first deals with utilizing silver-impregnated lumbar drains to prevent catheter bacterial colonization.[ 3 ] The second included chlorhexidine dressings to control scalp bacterial growth around the drain entry and exit points.[ 9 ]

The SiLuDrain trial

The SiLuDrain trial is a single-center RCT from Germany comparing infection and complication rates utilizing conventional versus silver-impregnated lumbar drains (both of 1.6-mm outer diameter and 0.8-mm inner diameter).[ 3 ] Forty-eight adults (24 per group, randomized in block sizes of 4, with no group crossovers) underwent lumbar drain placement. Reasons for placing drains included posthemorrhagic hydrocephalus, normal pressure hydrocephalus, and CSF fistulas. The following patients were excluded from the study: those with silver allergy, prior lumbar drain placements within 3 months, CSF infections, and leptomeningeal tumor spread. Patients did not receive periprocedural antibiotics.

Lumbar drain protocol

All patients had lumbar drains placed for an average of 4 days (range 1–10 days). Daily inspection of puncture sites was accompanied by routine CSF sampling on the day of drain placement and every 2nd day until drains were removed. Here, drain-associated CSF infection was defined as a confirmed cultured organism or clinical sign suggestive of meningitis. Patients in the silver-impregnated lumbar drain group experienced significantly fewer catheter-related complications [ Table 2 ]. Fewer patients (1 in the study group versus 4 in the control group, not statistically significant) experienced drain-associated CSF infections, diagnosed after 7 days of drain placement (range of 6–9 days). For the five patients with CSF infections, 14 CSF samples confirmed the growth of microorganisms (13 CSF cultures grew Staphylococcus species, one Gram-negative Escherichia coli, and one candida species). Ten of 14 Gram-positive CSF cultures showed significantly reduced bacterial growth when cultured in the presence of silver-impregnated catheters.


Table 2

Results from the SiLuDrain trial.

 

The external ventricular drain-associated infection (EVDAI) study

In Roethlisberger et al., single-center controlled RCT investigators studied scalp bacterial growth and silver-impregnated ventriculostomy colonization in patients with and without chlorhexidine wound dressings (chlorhexidine gluconate 2%).[ 9 ] Fifty-five adults, 28 in the study group and 27 in the control group, were randomized to undergo emergency ventriculostomy placements from 2013 to 2016. Exclusion criteria included CNS infections, posttraumatic dural breaches, and concomitant antimicrobial therapy. Patients underwent ventriculostomies in the operating theater, utilizing preprocedural cefuroxime and skin preparation of 30 s after hemicranial hair removal. They underwent silver-impregnated external ventricular drain placement utilizing 5 cm of subcutaneous tunneling of the catheter away from drain entry site.

Culture from the scalp

Sampling of scalp at drain exit sites was performed at the time of procedure for a skin area of 12 cm2, with dressing changes every 5 days. Those with silver-impregnated ventriculostomies placed for an average of 8 days (range 5–12 days), utilizing the chlorhexidine protocol, exhibited significantly less bacterial growth versus those with uncoated dressings [ Table 3 ]. More virulent Gram-positive cocci were detected for those with uncoated dressings. Given the small study cohort sizes, both groups showed nonsignificant differences in bacterial colonization of subcutaneous catheter segments, catheter tips, and ventriculostomy-associated infections.


Table 3

Results from the EVDAI study.

 

DISCUSSION

The SiLuDrain trial and EVDAI study offer insight regarding the prevention of drain-associated infections. The SiLuDrain trial demonstrated that silver-impregnated lumbar drains are well tolerated with fewer Gram-positive bacterial infections. Findings from this study are consistent with prior meta-analysis of prospective studies demonstrating the effectiveness of silver-coated ventricular drains in preventing ventriculostomy-associated infections.[ 2 , 5 - 7 ] Silver-coated catheters contain combinations of metallic silver and insoluble luminal silver salts with demonstrated patient safety profiles and antimicrobial properties.[ 4 , 5 , 10 ] Silver-coated drains may not be as effective as antibiotic-impregnated drains in preventing Gram-negative bacterial colonization. Dependent on the silver particle size, the positive charge of silver ions may be mitigated by negative charges of bacterial cell wall proteins as the duration of drain placement increases.[ 1 ]

Most drain-associated infections are caused by bacteria introduced at the time of drain insertion and subsequent catheter colonization, possibly as a result of scalp bacterial growth. The EVDAI study demonstrated reduced scalp bacterial growth, including fewer virulent Gram-positive strains, with the use of chlorhexidine wound dressings.[ 9 ] Despite this trial’s small sample size, it was methodologically well designed using silver-coated ventriculostomies as an effort to control for potential confounders associated with CSF infections.

Protocols for drain insertion and care can raise awareness of drain-associated CSF infection risk factors. Management of these risk factors, including multiple drain exchanges, frequent CSF samplings, and catheter duration, is essential to decrease patient morbidity and health-care-related costs associated with CSF infections and long-term likelihood of requiring permanent CSF diversion.

CONCLUSIONS

Two 2018 RCTs demonstrated that silver-coated drains were effective in decreasing Gram-positive bacterial adherence to catheter tips and subsequent colonization. They may not be as effective as antibiotic-impregnated drains in preventing Gram-negative bacterial colonization. Furthermore, antimicrobial-coated chlorhexidine dressings appear to be effective in suppressing scalp bacterial growth.

Disclaimer

The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Journal or its management.

References

1. Atkinson RA, Fikrey L, Vail A, Patel HC. Silver-impregnated external-ventricular-drain-related cerebrospinal fluid infections: A meta-analysis. J Hosp Infect. 2016. 92: 263-72

2. Atkinson R, Fikrey L, Jones A, Pringle C, Patel HC. Cerebrospinal fluid infection associated with silver-impregnated external ventricular drain catheters. World Neurosurg. 2016. 89: 505-9

3. Jakobs M, Klein S, Eigenbrod T, Unterberg AW, Sakowitz OW. The siLuDrain trial: A prospective randomized controlled trial comparing standard versus silver-impregnated lumbar drains. J Neurosurg. 2018. p. 1-8

4. Keong NC, Bulters DO, Richards HK, Farrington M, Sparrow OC, Pickard JD. The SILVER (Silver impregnated line versus EVD randomized trial): A double-blind, prospective, randomized, controlled trial of an intervention to reduce the rate of external ventricular drain infection. Neurosurgery. 2012. 71:

5. Konstantelias AA, Vardakas KZ, Polyzos KA, Tansarli GS, Falagas ME. Antimicrobial-impregnated and coated shunt catheters for prevention of infections in patients with hydrocephalus: A systematic review and meta-analysis. J Neurosurg. 2015. 122: 1096-112

6. Lackner P, Beer R, Broessner G, Helbok R, Galiano K, Pleifer C. Efficacy of silver nanoparticles-impregnated external ventricular drain catheters in patients with acute occlusive hydrocephalus. Neurocrit Care. 2008. 8: 360-5

7. Lemcke J, Depner F, Meier U. The impact of silver nanoparticle-coated and antibiotic-impregnated external ventricular drainage catheters on the risk of infections: A clinical comparison of 95 patients. Acta Neurochir Suppl. 2012. 114: 347-50

8. Ramanan M, Lipman J, Shorr A, Shankar A. A meta-analysis of ventriculostomy-associated cerebrospinal fluid infections. BMC Infect Dis. 2015. 15: 3-

9. Roethlisberger M, Moffa G, Fisch U, Wiggli B, Schoen S, Kelly C. Effectiveness of a chlorhexidine dressing on silver-coated external ventricular drain-associated colonization and infection: A prospective single-blinded randomized controlled clinical trial. Clin Infect Dis. 2018. 67: 1868-77

10. Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Michael Scheld W. 2017 infectious diseases society of America's clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017. 64: e34-65

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